Fig. 1

MRL/lpr mice develop anxiety-like phenotypes and reactive microglia before overt peripheral lesions. a Schematic of the experiment examining CNS lupus development in SLE mice. b–g Behavioral performance of 6-week-old and 16-week-old female MRL/lpr mice (red) and matched littermate controls (blue) in the open field test (OFT, b–d) and elevated plus-maze (EPM, e–g) test. n = 11-12 mice per group, Student’s unpaired t-test. h and i Representative IBA-1 immunofluorescence images of hippocampal sections (h). Scale bars, 80 μm and 10 μm under magnification. Immunostaining of CD68, a microglial/macrophage lysosomal activation marker, and IBA-1 in hippocampal sections from MRL/mpj and MRL/lpr mice (i). Scale bars, 20 μm. Arrows indicate reactive microglia. j and k Average microglial density in CA3 areas in control (blue) and MRL/lpr mice (red) (cells/mm²; n = 3-4 mice per group) (j). Quantitation of CD68⁺ microglia in hippocampal sections from MRL/mpj and MRL/lpr mice (n = 3–4 mice per group, with an average of 4-5 slices per mouse). l–n Representative image of IBA-1 in CA3 and complement C3 in kidneys from MRL/mpj and MRL/lpr mice at the indicated times; scale bars as indicated. Dot plots depicting the average number of IBA-1⁺ cells per mm² (m) and renal pathological score (n) quantified in control (blue) and MRL/lpr mice (red). n = 5 mice per group. The data are the mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001; and ns, not significant according to Student’s unpaired t-test. See also Supplementary Figs. 1 and 2